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Metabolic profiling Extraction and analysis of polar metabolites were performed as previously described 90,91 , with some modifications: 100 L of plasma were mixed with 1 mL of a pre-cooled (-20 C) homogenous methanol (MetOH):methyl-tert-butyl-ether (MTBE) 1:3 (v/v) mixture

On the subsequent days spheroids were washed in DMEM/F12 medium (Corning, USA) and the medium was changed, as follows: Basal medium: S1 MCDB131 (Corning, USA), 1% Glutamax (Thermo Fisher Scientific, Netherlands) + 1% Pen/Strep (Thermo Fisher Scientific, Netherlands), 2.44 mM glucose (Merck Millipore, USA), 29 mM sodium bicarbonate (Merck Millipore, USA), 2% BSA (Capricorn Scientific, USA), 2 l/100 mL ITS-X (Thermo Fisher Scientific, Netherlands)

Abbreviations ApoB: Apolipoprotein B-100 ApoC1: Apolipoprotein C1 ApoM: Apolipoprotein M FDR: False discovery rate GPX3: Glutathione peroxidase 3 HGFAC: Hepatocyte growth factor activator INNODIA: Innovative approaches to understanding and arresting type 1 diabetes LMM: Linear mixed model ND: Newly diagnosed SRM: Selected reaction monitoring UFM: Unaffected family member References Fyvie MJ, Gillespie KM (2023) The importance of biomarker development for monitoring type 1 diabetes progression rate and therapeutic responsiveness

Role in EGF receptor-mediated tyrosine phosphorylation

Gastric bypass surgery can reduce the stomachs ability to produce intrinsic factor, a protein needed for B12 absorption